The primary objective of this research program is to study mechanisms of immunocyte differentiation, antigen recognition and T cell-B, macrophage-T cell interaction in humoral and cellular immune responses. This objective will be accomplished through our continued investigation of the relationship of these immunoloic functions to histocompatibility linked I-region gene products - Ia antigens. Experiments performed during the initial period of this grant demonstrated a unique role for I-J region gene products expressed on the antigen presenting macrophage in macrophage-T cell interaction. The continuation of this project is designed to determine the repertoire of Ia specificities present on macrophages, whether there are functionally different macrophages with different Ia markers and the mechanism of I-J region gene product function in antigen presentation and macrophage-T cell interaction. Highly restricted anti-Ia sera will be uses as probes to look directly at membrane structures coded for by I region genes. These sera, together with specific anti-idiotypic sera prepared against idiotypic determinants of anti-Ia antibodies, will be used to study the mechanisms of immune response induction at the level of the macrophage. In addition, highly purified subpopulations of macrophages, T cells and B cells will be used in various allogeneic combinations across I subregion differences to look at requirements of genetic restriction for successful macrophage-T cell cooperation in primary and secondary antibody responses. Parallel experiments will utilize antigen induced T cell proliferative responses for comparison.